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Sutter Pacific Medical Foundation Physician's Study Focuses on Gene's Role in Skin Cancer

Mohammed Kashani-Sabet, M.D., Sutter Pacific Medical Foundation, published a study in the prestigious Proceedings of the National Academy of Sciences. Study findings could lead to targeted therapies for melanoma and other cancers with this gene.

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PRLog (Press Release) - Apr. 26, 2012 - Research on Gene’s Role in Melanoma Could Help Lead to Targeted
Therapies for Cancer

(San Francisco, CA, April 26, 2012) – Researchers at California Pacific Medical Center Research Institute (CPMCRI), part of the Sutter Health network, have found that increased expression of a gene in the deadly skin cancer melanoma can increase the risk of death from the tumor, and represents a possible new target for treatment of melanomas that express high levels of this gene. The findings will be published in Proceedings of the National Academy of Sciences (PNAS).

It is the first time the role of PHIP, pleckstrin homology domain-interacting protein, has been reported in any cancer, according to the study. The findings could lead to new therapies for treating melanoma and other types of cancer where PHIP is active. The study, “Pleckstrin Homology Domain-Interacting Protein (PHIP) as a Marker and Mediator of Melanoma Metastasis,” is scheduled for publication in the online edition of PNAS the week of April 16, 2012. The paper also will appear in the print edition of PNAS.

“We’ve shown that this gene is a marker of increased risk of spread and of death due to  melanoma,’’ said Mohammed Kashani-Sabet, MD, a dermatologist at Sutter Pacific Medical Foundation, director of the Center for Melanoma Research and Treatment at California Pacific Medical Center and the study’s senior author. “Studying this gene helps us to understand which melanomas are more aggressive. The hope is that further study will lead to targeted treatments for melanoma and other cancers.”

Researchers examined the effects of high levels of the PHIP protein on the spread or metastasis of melanoma both in mice and in human tissues from melanoma patients, and showed that tumors with higher expression of PHIP were associated with reduced survival in both of these studies. For example, researchers suppressed PHIP in melanomas in mice, and they found that mice in this category lived longer than the mice that had melanomas with active PHIP.

In addition, the researchers studied tissues from a cohort of 345 patients with   melanoma. They found that nearly one-third of them had the highest levels of PHIP, which correlated with significantly reduced survival when compared with melanomas with lower levels of PHIP expression.

“We learned in both mice and humans, that the more of this (PHIP) a tumor has, the  higher the risk is for the cancer spreading and the lower the survival,” Kashani-Sabet said.

The researchers also considered the genetic makeup of melanoma tumors to understand which melanomas might carry increased amounts of PHIP. Recent studies have centered on the role of other genes in melanoma, particularly, the gene known as BRAF. BRAF is mutated in about 50 percent of melanomas. An inhibitor of mutated BRAF prolonged the survival of patients with metastatic melanoma, and was approved by the U.S. Food and Drug Administration in 2011. However, the genes that are responsible for the metastasis of melanomas without this mutation are unknown, and few effective therapies exist for patients whose melanomas do not have a BRAF mutation.

In this study, high PHIP levels were specifically found in melanomas without a    mutation in BRAF. In fact, many melanomas with high levels of PHIP also lacked mutations in two other important genes called NRAS and PTEN. Therefore, PHIP may be responsible for the aggressive behavior of "triple-negative" melanomas that do not have these common gene mutations, researchers say.

The finding is significant because researchers hope that future therapies for patients with melanoma and other cancers can be developed by targeting a gene such as PHIP that promotes spread of the tumor.

Next steps include confirming that PHIP is a marker for melanomas in human tissue specimens from other institutions and other countries, Kashani–Sabet said. He also plans to study other cancers where PHIP may play an important role.

California Pacific Medical Center. Hands-on Healing.
At San Francisco’s California Pacific Medical Center we deliver personal, hands-on care to every single patient, every single day. As one of California’s largest private, community-based, not-for-profit, teaching medical centers, we research the most up-to-date treatments, hire the most qualified individuals, and practice the most modern, innovative medicine available. We deliver the highest quality expert care, with kindness and compassion, in acute, post-acute and outpatient services, as well as preventive and complementary medicine. We also provide disease counseling, family support and wellness treatments. Throughout the entire organization, every member of the CPMC team is committed to giving our patients the individual, hands-on attention they deserve. Every hand plays a part, and every hand has the power to change a life. www.cpmc.org

About Sutter Pacific Medical Foundation
Sutter Pacific Medical Foundation is a group of 240+ doctors who offer primary, specialty and complex medical care.  Our physicians in San Francisco, Marin, Sonoma, Lake and Del Norte counties combine the latest in medical technology with personalized care.  As part of the Sutter Health not-for-profit network, Sutter Pacific doctors are affiliated with some of the most respected hospitals in the region and provide care in local communities. For more information or to find a doctor near you, visit www.sutterpacific.org or call 1-888-699-DOCS (3627).

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Source:Sutter Pacific Medical Foundation
Country:United States
Industry:Health
Tags:Sutter Pacific Medical Foundation, Research, Mohammed Kashani-Sabet, m d, melanoma, California Pacific Medical Center
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